Pain is the most common symptom for which patients seek medical assistance and relief, and chronic pain is among the most vexing problems that physicians face. In general, pain has two aspects: the first is a non-emotional perception of a stimulus or event which is usually strong enough to produce tissue damage to the person; the second is the individual's personal response to the perception of that stimulus or event. Pain implies damage to the human organism, whether physical or psychological; and chronic pain, if untreated, will itself cause damage to the living body.
For these reasons, the clinician normally questions his patient regarding the characteristics of the pain. A carefully elicited history of pain will include the chronology, nature, location, radiation of pain, and any other factors that aggravate or alleviate pain. Pain is a highly subjective phenomenon and the patient's description may often be difficult to interpret objectively. Individual reactions to pain are extremely variable, often being influenced by many psychosocial and cultural factors. It is therefore essential for the clinician to establish not only the primary cause (e.g., trauma or infection) and pathogenesis (e.g., inflammation or anoxia) of the pain, but also any significant contributing factors (e.g., anxiety or secondary gain).
Symptomatically, pain may be local or diffuse; constant or intermittent; sharp or dull; and acute or chronic. The sensing organs for pain are the naked nerve endings found in almost every tissue of the body. Pain impulses are transmitted to the central nervous system by two fiber systems. One system is made up of small, myelinated somatic nerve fibers which conduct pain quickly; the other comprises unmyelinated nerve fibers which conduct pain impulses more slowly. The presence of these two pain pathways, one slow and one fast, has been proposed as the explanation for the physiological observation that there are two kinds of pain. A painful stimulus causes a "bright, sharp, localized" sensation which is typically followed by a "dull, intense, diffuse" unpleasant feeling. These two sensations are variously called fast and slow pain or first and second pain.
Pain is also clinically identified as being either acute or chronic. A common view holds that the difference between acute and chronic pain can be described by the duration of the pain. Pain lasting over six months in duration is typically considered chronic; and any shorter time period of pain is usually considered acute. Several other clinical features are also traditionally used to differentiate acute pain from chronic pain. Patients suffering from severe acute pain often give a clear description of its location, character, and timing. Also, acute pain usually responds well to analgesic agents; and the psychological makeup of the patient often plays only a minor role in the pathogenesis. In contrast, patients suffering from chronic pain typically are unable to describe precisely the location, character, and timing of the pain. Furthermore, chronic pain often is less responsive to analgesic agents; and the individual's psychologic state has a larger role. The clinician's dilemma thus is increased since there are no reliable, objective tests by which to assess chronic pain. For the reasons, the physician normally accepts his patient's report, taking into consideration his age, cultural background, environment, and other psychologic background factors known to alter a person's subjective reaction to pain.
Physicians also conventionally divide chronic pain into three somewhat overlapping categories in decreasing order of frequency. These are: psychophysiological disorders; chronic pain associated with structural disease; and somatic delusions. Psychophysiological disorders are those in which psychological factors have engendered chronic physiological alterations which produce pain long after the underlying cause has healed. Structural disease, such as a herniated disc or torn ligament, may once have been present; but whether structural disease was ever present or not, the pain continues chronically long after the organic disorder has disappeared. Such persons tend to respond poorly to analgesic drugs, but often respond well to combination therapy directed against the organ tissue and at the disturbing psychological factors.
Chronic pain associated with structural disease may be characterized by prolonged episodes of pain such as occurs with rheumatoid arthritis, metastatic cancer, or sickle cell anemia. The patient may have prolonged episodes of pain alternating with pain-free intervals; or display unremitting pain which varies in severity. Psychological factors may play an important role in increasing or relieving pain, but the treatment of the chronic pain by analgesics or correcting the underlying disease is typically more helpful.
The category of somatic delusions represents pain caused by neither structural nor physiological disorders. Such pain occurs in patients with profound psychiatric disturbances such as psychotic depression or schizophrenia. The history of the pain is so vague and bizarre and the distribution of the pain is typically so unanatomical as to suggest this category. Such persons respond only to psychiatric therapy; and the management of pain must be pursued with this causation in mind. It will be recognized that these divisions represent the conventional theoretical classifications of chronic pain for purposes of clinical diagnosis of painful disorders.
The physician confronted with a person complaining of chronic pain thus normally follows the accepted principles for providing pain relief. These commonly include correcting the cause of pain; individualizing therapeutic treatment; and selecting appropriate analgesics. Clearly, measures directed at eliminating the true cause of pain deserve the first consideration. Pain relief can only be achieved by modifying or suppressing the primary disease process; and the hazards of administering analgesics without first attempting to establish a diagnosis can not be overemphasized. Analgesics, particularly narcotics, may mask the symptoms of serious illness.
The symptomatic management of pain is dependent upon its severity and cause. The relief of chronic pain is often perplexing and difficult because measures useful in the treatment of acute pain are often ineffective for chronic pain. It is often necessary to resort to a combination of indirect and multidisciplinary therapeutic methods in order to provide any sort of relief whatsoever. These include the following:
Analgesics: The use of analgesics includes nonaddictive formulations, narcotics, and sometimes antidepressant drugs in low doses. The nonaddictive analgesics employed include salicylates such as aspirin; acetominophen; and newer nonsteroidal, anti-inflammatory drugs such as indoleacetic acids, oxicams, and proprionic acids. The potentially addictive analgesics include codeine, propoxyphene, agonist-antagonist opioids; and morphine. The antidepressant drugs include monoamine oxidase inhibitors; tricyclic antidepressants; or the newer cyclic drugs which include maprotiline, trazodone, and nomifensine [Clinical Pharmacokinetics of Analgesic Drugs, (Prithri, R. P., editor), Yearbook Medicall Publishers, 1986, pp 503-538].
A second approach to alleviating chronic pain utilizes the numerous psychological techniques such as hypnosis, operant conditioning, biofeedback, progressive relaxation, distraction, and placebo therapy. Each of these have had varying degrees of success in relieving chronic pain [Textbook of Pain, (Wall and Melzack, editors), 2nd edition, 1989, pp 989-1031].
A third approach has been the use of transcutaneous electrical nerve stimulation or "TENS" of which many varieties of apparatus are commercially available today. This technique employs the use of electric current to stimulate the peripheral or central nerves of the body and is said to be a simple and effective means of relieving well-localized chronic pain for some patients Unfortunately, the success and relief of pain varies markedly from person to person [Deyo et al., New Eng. J. Med 322:1627-1634 (1990)].
A recently adopted procedure for chronic pain treatment employs acupuncture. While the mechanism of relief remains uncertain (and sometimes criticized by different medical authorities), the use of acupuncture sometimes does provide relief for the chronic sufferer [Textbook of Pain, (Wall and Melzack, editors), 2nd edition, 1989, pp 906-919].
A variety of different neurosurgical procedures including chordotomy and deep brain electrical stimulation are sometimes considered where the patient has severe, chronic pain. The value of these procedures for the treatment of chronic pain is unfortunately often in doubt [Textbook of Pain, (Wall and Melzack, editors), 2nd edition, 1989, pp 768-883].
A more common procedure often employed is the use of sympathetic nerve blockade in which local anesthetic agents reversibly block nerve impulse conduction when introduced into the central nervous systems. Via different techniques, the local anesthetic agent is applied to sympathetic nerves in the subarachnoid space, the epidural space, or ganglia by syringe. These procedures and techniques have been employed for approximately seventy years as treatments for intractable visceral pain states such as chronic pancreatic pain or chronic pain from a visceral malignancy [Management of Pain, (Bonica, J. J., editor), Lea and Febiger, 1953, pp 371-456].
In addition to all the forgoing approaches and techniques described, the scientific literature is replete with reports of experiments and unusual techniques for the treatment of chronic pain syndromes. The difficulty with such reported techniques and modes of chronic pain treatment is that the reported experiment or history of chronic pain treatment is not viewed by other practitioners, physicians, or medical research as a viable alternative; and the isolated report and technique remains limited both in usage and availability to only a few persons outside the original research group which first identified it for use.
To factually demonstrate this anomaly, the treatment of chronic pain via iontophoresis of vinca alkaloids onto the skin of patients stands as but one outstanding example. Of the four chemically similar vinca alkaloids, only two--vinblastine and vincristine, have recently received some clinical investigation. The vinca alkaloids are extracts of the periwinkle plant and were first recognized to show activity against an acute lymphocytic neoplasm in mice. The therapeutic uses clinically produce beneficial responses in various lymphomas and leukemias and act as agents against carcinomas of the breast, lung, oral cavity, testis, and bladder. In the early 1980's, a Hungarian research group reported the treatment of chronic pain syndrome using iontophoresis of vinca alkaloids [Csillik et al., Neuroscience Letters 31:87-90 (1982)]. Subsequently, a report of iontophoresis administration of vinca alkaloids in the treatment of postherpetic pain was published by an Italian research group [Rossano et al., The Pain Clinic 3:31-36 (1989)]. Each publication reported the effective treatment of pain for its patients without causing major physiological changes. Neither publication and report was able to go beyond the immediate clinical treatments described; and insofar as is presently known, there has been no follow up whatsoever either to confirm or improve the basic reports described within each of these publications.
The major difficulties, therefore, with all the previously described conventionally known techniques said to be effective in the treatment of chronic pain are thus two-fold in nature. First, the primary purpose for most of the conventionally known procedures and therapeutic regimens is intended for the treatment of acute pain primarily--the techniques of which have then been fostered onto the treatment of patients with chronic pain as an additional possible application. Accordingly, none of the conventionally known treatments were intended for use in the treatment of chronic pain specifically; and none are directed to alleviating the poorly localized, ill defined character, and inconsistent timing of chronic pain. Second, as generally recognized and appreciated by clinicians and medical researchers alike, the conventionally known therapeutic treatments and regimens for treating chronic pain are highly subjective and individual in their efficacy; irregular and inconsistent in providing any relief whatsoever; and are as likely to fail as to succeed in providing any pain relief at all.
It is precisely for this failure to expect good results that many medical authorities strongly advise and recommend the use of a combination of indirect and multidisciplinary therapeutic methods--none of which is expected to work alone and very few of which are consistently effective even in combination. The clinician must proceed in a trial and error mode approach in treating the chronic pain sufferer, eliminating those which appear to provide little or no relief while concentrating and emphasizing those which sporadically appear to provide some therapeutic effect. Worst of all, it is generally agreed among practitioners and clinicians that despite all of the presently known methods and techniques, a very substantial number of persons suffering from chronic pain will find no meaningful relief whatsoever; and be compelled merely to endure the chronic pain as best they can. For all these reasons, it will be recognized and appreciated that a therapeutic method will provide effective and immediate long-term relief to person afflicted with chronic pain would be seen as an outstanding advance and major improvement in therapeutic methods.